PTEN-related Disorders 

Mutations in PTEN can cause many different disorders, including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. They can also cause autism spectrum disorders with macrocephaly, congenital malformations, and/or increased risks for cancer.
Quick Reference
Test Code: 2102 Test Name: PTEN specific site analysis TAT: 7-14 days Genes: 1
Test Code: 2106 Test Name: PTEN seq and del/dup TAT: 14-21 days Genes: 1

Ordering Options

We offer family variant testing at no additional cost

We offer family variant testing for all blood relatives of patients who undergo full single gene sequencing, multigene panel testing or exome sequencing at Ambry Genetics and are found to have a pathogenic or likely pathogenic variant. Testing must be completed within 90 days of the original report date. Whenever possible, more closely related relatives should be tested before more distant relatives. If you or a family member are interested in learning more about our family testing program or when family testing may be clinically indicated, please contact us or your provider for additional information. Note that Ambry can only provide such family testing services to patients receiving medical care in the U.S or US territories.

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Why Is This Important?

  1. Option to modify frequency and initial age of mammogram/breast MRI, colonoscopy, or other screening as appropriate
  2. Consideration of prophylactic mastectomy or other risk-reducing measures, as appropriate 
  3. Identify at-risk family members 

When To Consider Testing

Major and minor criteria (see detailed list below) have been established based on the features of PHTS and are used for testing and clinical diagnostic criteria.1 

Individuals with one or more of the following may be appropriate candidates for PTEN genetic testing: 

  • 2 or more major criteria, with one being macrocephaly
  • 3 major criteria without macrocephaly
  • 1 major and ? 3 minor criteria
  • ? 4 minor criteria  
  • American College of Medical Genetics and Genomics recommends PTEN testing for any child with an autism spectrum disorder and macrocephaly.2
  • A personal history of BRRS 
  • ? 2 biopsy proven trichilemmomas
  • Features that meet clinical diagnostic criteria for CS/PHTS
  • Family history of a known PTEN mutation
  • Lhermitte-Duclos disease, even in the absence of other signs of PHTS

Mutation Detection Rate

PTEN mutations can be found in ~85% of individuals with CS, 65% of individuals with BRRS, and 20% of individuals with PS. Furthermore, gross deletions have been found in 10% of individual with BRRS and/or CS-like syndrome (clinical sensitivity).

In the setting of an autism spectrum disorder, PTEN mutations have been reported in~5% of patients who also have macrocephaly, and another 12% of patients diagnosed with developmental delay or intellectual disability (clinical sensitivity).2

Ambry's PTEN analysis can detect >99.9% of described mutations in the gene, when present (analytic sensitivity).

Test Description

PTEN coding exons 1-9 and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for coding exons 1-9. Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology, using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Potentially homozygous variants, variants in regions complicated by pseudogene interference, and variant calls not satisfying depth of coverage and variant allele frequency quality thresholds are verified by Sanger sequencing. Gross deletion/duplication analysis of PTEN using read-depth from NGS data is also performed. Any copy number changes detected by NGS are confirmed by targeted chromosomal microarray and/or multiplex ligation-dependent probe amplification (MLPA). 

1. Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTENHamartoma Tumor Syndrome; systematic review and revised diagnsotic criteria.  J Natl Cancer Inst.2013; 105:1607-1616.

2. Herman GE, Henninger N, Ratliff-Schaub K, Pastore M, Fitzgerald S, McBride KL. Genetic testing in autism: how much is enough? Genet Med. 2007;9(5):268-74.

3. McBride KL, Varga EA, Pastore MT, Prior TW, Manickam K, Atkin JF, et al. Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly. Autism Research. 2010;3(3):137-41.


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